By replacing the Jκ segments of the mouse Ig gene with a human VJ exon/neomycin cassette, all endogenous rearrangement is blocked, which leads to the production of chimeric human VJ/mouse κ constant LC. Breeding with DH-LMP2A mice ensures the production of only free LCs by all B and plasma cells. The high serum concentrations of a monoclonal κ-free LC produced in the development of LC deposition disease is reminiscent of the human disease at 6 months.